Cigarette smoking is the leading, preventable cause of morbidity and mortality among women; however, approximately 18 percent of women continue to smoke cigarettes. Mood-related withdrawal symptoms and concerns about weight-gain are significant barriers to successful smoking cessation, especially among women. Moderate intensity exercise (e.g., brisk walking) is a safe and low-cost adjunct to standard smoking cessation treatments that may aid in the smoking cessation process by improving mood and attenuating weight concerns during smoking cessation. Previous RCTs examining moderate intensity exercise as a smoking cessation treatment have been plagued by poor compliance with the exercise program, lack of adequate control conditions, and lack of objective monitoring of exercise behavior and smoking cessation outcomes. Thus, we propose an RCT (N = 164) to test the efficacy of moderate intensity exercise (150 min/week) as an adjunct to a standard 12-week smoking cessation treatment (i.e., brief one-time baseline counseling plus the nicotine patch) among healthy, previously inactive adult female smokers. Consistent with our recently completed pilot study (R03 CA119747), a number of techniques will be used to enhance internal validity and thus overcome the weaknesses of previous trials, including: (a) use of a wellness comparison condition that equates for staff contact time; (b) direct observation of all exercise and wellness sessions; (b) use of monetary incentives to increase compliance with the exercise/wellness programs; and (c) multiple objective assessments of smoking status (CO monitoring and saliva cotinine analysis) during the 12-week treatment and during a 6-month follow- up period. Additionally, we will explore affective withdrawal symptoms and weight concerns as potential mechanisms of the exercise treatment in real-time and in participants natural environments via ecological momentary assessment. The proposed study will provide a definitive test of the efficacy of moderate intensity exercise as an adjunct to standard smoking cessation treatment. If initial efficacy can be established, then further research will be warranted to test more disseminable moderate intensity exercise programs to establish effectiveness in real-world conditions (i.e., enhancing adherence to exercise programs in the absence of monetary incentives). Regardless of treatment outcomes, the proposed EMA protocol will provide a rich source of data to conduct a detailed examination of the determinants of smoking lapses and relapse over time and how these determinants are impacted by exercise behavior. This will further our understanding of successful smoking cessation versus relapse and aid in the design of future smoking cessation interventions. PUBLIC HEALTH RELEVANCE: Cigarette smoking is the leading, preventable cause of death and disease among women. Moderate intensity exercise (i.e., brisk walking) may improve the efficacy of standard smoking cessation programs, such as the nicotine patch, especially among women. This study will compare the effects of 12 weeks of moderate intensity exercise (150 min/week) plus the nicotine patch versus 12 weeks of a video-based wellness program plus the nicotine patch on smoking cessation outcomes and nicotine withdrawal symptoms among 164 healthy, previously inactive, female smokers.